Biomedical Engineering Reference
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incorporated, myocardial performance was improved. The ability to regenerate
functioning muscle after autologous myoblast transplantation could have an impor-
tant effect on patients after acute MI.
After MI, adverse remodeling with left ventricular dilatation is a major determi-
nant of poor outcome. Skeletal myoblast implantation improves cardiac function
post-MI by modulation of adverse remodeling, and this effect can be significantly
enhanced by targeting IL-1 as a key upstream regulator of both adverse remodeling
and graft cell death. Several studies have shown that implanted skeletal myoblasts
form viable grafts in infarcted myocardium, resulting in enhanced post-MI exercise
capacity and contractile function with attenuated ventricular dilation. These data
illustrate that syngeneic myoblast implantation after MI improves both in vivo and
ex vivo indexes of global ventricular dysfunction and deleterious remodeling and
suggests that cellular implantation may be beneficial after MI. Skeletal autologous
myoblasts have been the first cells to be used clinically in patients with advanced
ischemic heart failure as they feature several advantages. Preliminary data from a
phase I clinical trial suggested the feasibility and safety of autologous skeletal
myoblast transplantation in severe ischemic cardiomyopathy.
The Myoblast Autologous Graft in Ischemic Cardiomyopathy (MAGIC) trial
was designed to test whether autologous skeletal myoblasts can be used to reverse
damage done to cardiac muscle following a heart attack, or to safely halt a patient's
further progression of heart failure. Patients who participated in the study had isch-
emic heart failure. A previous blockage in one of their coronary arteries caused a
heart attack, creating a serious defect in the wall of their left ventricle (LV). Patients
were also diagnosed with an additional blockage in a coronary artery requiring
coronary artery bypass grafting (CABG) surgery. In the study, one of two doses of
autologous skeletal myoblasts or placebo were injected during CABG surgery in
and around the scar tissue caused by the heart attack to attempt to strengthen the
defect in the ventricular wall. Patients were enrolled at sites in France, UK, Italy,
Belgium, and Germany. All patients received an implantable cardioverter-defibrillator.
The primary efficacy end points were the 6-month changes in global and regional
LV function assessed by echocardiography. The safety end points comprised a
composite index of major cardiac adverse events and ventricular arrhythmias.
It was concluded that myoblast injections combined with CABG in patients with
depressed LV function failed to improve echocardiographic heart function
(Menasché et al.
2008
). The increased number of early postoperative arrhythmic
events after myoblast transplantation, as well as the capability of high-dose injections
to revert LV remodeling, warrants further investigation.
Patching Myocardial Infarction with Fibroblast Culture
Revascularization of damaged myocardium represents an important therapeutic
goal in patients with coronary artery disease. Pharmacologically induced revascu-
larization with VEGF and bFGF has been successful in stimulating new microvessel
growth or an increase in myocardial collateral blood flow.
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